There’s nothing new about cannabis, of course. It’s been around humankind pretty much forever.
In Siberia charred seeds have been found inside burial mounds dating back to 3000 B.C. The Chinese were using cannabis as a medicine thousands of years ago. Marijuana is deeply American too—as American as George Washington, who grew hemp at Mount Vernon. For most of the country’s history, cannabis was legal, commonly found in tinctures and extracts.
Then came Reefer Madness. Marijuana, the Assassin of Youth. The Killer Weed. The Gateway Drug. For nearly 70 years the plant went into hiding, and medical research largely stopped. In 1970 the federal government made it even harder to study marijuana, classifying it as a Schedule I drug—a dangerous substance with no valid medical purpose and a high potential for abuse, in the same category as heroin. In America most people expanding knowledge about cannabis were by definition criminals.
But now, as more and more people are turning to the drug to treat ailments, the science of cannabis is experiencing a rebirth. We’re finding surprises, and possibly miracles, concealed inside this once forbidden plant. Although marijuana is still classified as a Schedule I drug, Vivek Murthy, the U.S. surgeon general, recently expressed interest in what science will learn about marijuana, noting that preliminary data show that “for certain medical conditions and symptoms” it can be “helpful.”
In 23 states and the District of Columbia cannabis is legal for some medical uses, and a majority of Americans favor legalization for recreational use. Other countries are rethinking their relationship to pot too. Uruguay has voted to legalize it. Portugal has decriminalized it. Israel, Canada, and the Netherlands have medical marijuana programs, and in recent years numerous countries have liberalized possession laws.
Ganja is simply around us more, its unmistakable but increasingly unremarkable smell hanging in the air. Yes, smoking it may lead to temporary laughing sickness, intense shoe-gazing, amnesia about what happened two seconds ago, and a ravenous yearning for Cheez Doodles. Though there’s never been a death reported from an overdose, marijuana—especially today’s stout iterations—is also a powerful and in some circumstances harmful drug.
Still, for many, cannabis has become a tonic to dull pain, aid sleep, stimulate appetite, buffer life’s thumps and shocks. Pot’s champions say it peels back layers of stress. It’s also thought to be useful as, among other things, an analgesic, an antiemetic, a bronchodilator, and an anti-inflammatory. It’s even been found to help cure a bad case of the hiccups. Compounds in the plant, some scientists contend, may help the body regulate vital functions—such as protecting the brain against trauma, boosting the immune system, and aiding in “memory extinction” after catastrophic events.
In the apparent rush to accept weed into the mainstream, to tax and regulate it, to legitimize and commodify it, important questions arise. What’s going on inside this plant? How does marijuana really affect our bodies and our brains? What might the chemicals in it tell us about how our neurological systems function? Could those chemicals lead us to beneficial new pharmaceuticals?
If cannabis has something to tell us, what’s it saying?
Even into the middle of the 20th century, science still didn’t understand the first thing about marijuana. What was inside it and how it worked remained a mystery. Because of its illegality and tainted image, few serious scientists wanted to besmirch their reputations by studying it.
Then one day in 1963 a young organic chemist in Israel named Raphael Mechoulam, working at the Weizmann Institute of Science outside Tel Aviv, decided to peer into the plant’s chemical composition. It struck him as odd that even though morphine had been teased from opium in 1805 and cocaine from coca leaves in 1855, scientists had no idea what the principal psychoactive ingredient was in marijuana. “It was just a plant,” says Mechoulam, now 84. “It was a mess, a mélange of unidentified compounds.”
So Mechoulam called the Israeli national police and scored five kilos of confiscated Lebanese hashish. He and his research group isolated—and in some cases also synthesized—an array of substances, which he injected separately into rhesus monkeys. Only one had any observable effect. “Normally the rhesus monkey is quite an aggressive individual,” he says. But when injected with this compound, the monkeys became emphatically calm. “Sedated, I would say,” he recalls with a chuckle.
Further testing found what the world now knows: This compound is the plant’s principal active ingredient, its mind-altering essence—the stuff that makes you high. Mechoulam, along with a colleague, had discovered tetrahydrocannabinol (THC). He and his team also elucidated the chemical structure of cannabidiol (CBD), another key ingredient in marijuana, one that has many potential medical uses but no psychoactive effect on humans.
For these breakthroughs and many others, Mechoulam is widely known as the patriarch of cannabis science. Born in Bulgaria, he is a decorous man with wispy white hair and watery eyes who wears natty tweeds, silk scarves, and crisp dress slacks. He’s a respected member of the Israel Academy of Sciences and Humanities and an emeritus professor at Hebrew University’s Hadassah Medical School, where he still runs a lab.
The author of more than 400 scientific papers and the holder of about 25 patents, this kindly grandfather has spent a lifetime studying cannabis, which he calls a “medicinal treasure trove waiting to be discovered.” His work has spawned a subculture of cannabis research around the globe. Though he says he’s never smoked the stuff, he’s a celebrity in the pot world and receives prodigious amounts of fan mail.
“It’s all your fault,” I say to him when we meet in his book-lined, award-crammed office to discuss the explosion of interest in the science of marijuana.
“Mea culpa!” he replies with a smile.
Israel has one of the world’s most advanced medical marijuana programs. Mechoulam played an active role in setting it up, and he’s proud of the results. More than 20,000 patients have a license to use cannabis to treat such conditions as glaucoma, Crohn’s disease, inflammation, appetite loss, Tourette’s syndrome, and asthma.
Despite that, he’s not particularly in favor of legalizing cannabis for recreational use. He doesn’t think anyone should go to jail for possessing it, but he insists that marijuana is “not an innocuous substance”—especially for young people. He cites studies showing that the prolonged use of high-THC strains of marijuana can change the way the developing brain grows. He notes that in some people cannabis can provoke serious and debilitating anxiety attacks. And he points to studies that suggest cannabis may trigger the onset of schizophrenia among those who have a genetic predisposition to the disease.
If he had his way, what Mechoulam regards as the often irresponsible silliness of recreational pot culture would give way to an earnest and enthusiastic embrace of cannabis—but only as a medical substance to be strictly regulated and relentlessly researched. “Right now,” he complains, “people don’t know what they’re getting. For it to work in the medical world, it has to be quantitative. If you can’t count it, it’s not science.”
In 1992 Mechoulam’s quest for quantification led him from the plant itself to the inner recesses of the human brain. That year he and several colleagues made an extraordinary discovery. They isolated the chemical made by the human body that binds to the same receptor in the brain that THC does. Mechoulam named it anandamide—from the Sanskrit for “supreme joy.” (When asked why he didn’t give it a Hebrew name, he replies, “Because in Hebrew there are not so many words for happiness. Jews don’t like being happy.”)
Since then several other so-called endocannabinoids and their receptors have been discovered. Scientists have come to recognize that endocannabinoids interact with a specific neurological network—much the way that endorphins, serotonin, and dopamine do. Exercise, Mechoulam notes, has been shown to elevate endocannabinoid levels in the brain, and “this probably accounts for what jogging enthusiasts call runner’s high.” These compounds, he explains, apparently play an important role in such basic functions as memory, balance, movement, immune health, and neuroprotection.
Typically, pharmaceutical companies making cannabis-based medicines have sought to isolate individual compounds from the plant. But Mechoulam strongly suspects that in some cases those chemicals would work much better in concert with other compounds found in marijuana. He calls this the entourage effect, and it’s just one of the many cannabis mysteries that he says require further study.
“We have just scratched the surface,” he says, “and I greatly regret that I don’t have another lifetime to devote to this field, for we may well discover that cannabinoids are involved in some way in all human diseases.”
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